Metabolic memory of -cells controls insulin secretion and is mediated by CaMKIIa.pdf.pdf

munication
Metabolic memory of ß-cells controls insulin
secretion and is mediated by CaMKIIa
Gustavo Jorge dos Santos 1,2, Sandra Mara Ferreira 1, Fernanda Ortis 1,3, Luiz Fernando Rezende 1,
Chengyang Li 4, Ali Naji 4, Everardo Magalhães Carneiro 1, Klaus H. Kaestner 2,**, Antonio Carlos Boschero 1,*
ABSTRACT
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Ca2 /calmodulin-dependent protein kinase II (CaMKII) functions both in regulation of insulin secretion and neurotransmitter release through
common downstream mediators. Therefore, we hypothesized that pancreatic ß-cells acquire and store the information contained in calcium
pulses as a form of “metabolic memory”, just as neurons store cognitive information. To test this hypothesis, we developed a novel paradigm of
pulsed exposure of ß-cells to intervals of high glucose, followed by a 24-h consolidation period to eliminate any acute metabolic effects.
Strikingly, ß-cells exposed to this high-glucose pulse paradigm exhibited significantly stronger insulin secretion. This metabolic memory was
entirely dependent on CaMKII. Metabolic memory was reflected on the protein level by increased expression of proteins involved in glucose
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sensing and Ca2 -dependent vesicle secretion, and by elevated levels of the key ß-cell transcription factor MAFA. In summary, like neurons,
human and mouse ß-cells are able to acquire and retrieve information.
Ó 2014 The Authors.